Interleukin-2-mediated modulation of plasma cell tumor growth in a model of multiple myeloma.
A number of studies have demonstrated that inoculation of certain types of cancer cells engineered for expression of the interleukin-2 (IL-2) gene results in reduced tumorigenicity and/or protection from subsequent challenge with a tumorigenic dose of wild-type cells. In the current studies, we have employed murine plasma cell tumors to examine IL-2-mediated tumor rejection as a possible model for therapeutic approaches to human myeloma or plasma cell leukemia. Two murine plasma cell tumor lines, S107 and X24, were infected with a retroviral vector expressing the human IL-2 gene, and the antitumor potential of IL-2-expressing infectants was characterized in syngeneic BALB/c and BALB/c nu/nu mice. Results demonstrate that tumorigenicity of both lines correlates inversely with the amount of IL-2 produced by the tumor cells. However, there are clear differences between the two lines in terms of reduced tumorigenicity and the ability to protect against co-injected parental tumor cells that appear unrelated to IL-2 levels. More importantly, intravenous immunization of animals with irradiated, IL-2 secreting cells from either line leads to significant protection from challenge with highly metastatic parental cells. These results suggest that such an approach may warrant consideration in the treatment of human plasma cell dyscrasias.
Kopantzev
E
E
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Roschke
V
V
Rudikoff
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D007376:Interleukin-2